基于锰增强磁共振和MAPK通路的耳聋人工耳蜗植入后脑可塑性重组机制研究

Recent evidence suggests that neural development and cross-modal reorganization of the auditory nervous system in the deaf after cochlear implant (CI) have a significant impact on the hearing and speech rehabilitation. However, the relationship between the duration of deafness and reorganization in the development, structure, and function of brain after CI and possible mechanism still remain unclear. Addressing this issue is critical to understanding the possible mechanism of different effect of rehabilitation in the congenital deaf after CI, is useful for providing new information for adjusting the existing CI policy decisions to improve the effect of rehabilitation, and can also provide a new platform and evidence to study sensory input dependent cortical plasticity. Therefore, we will use manganese-enhanced MRI (MEMRI) to investigate the relationship between the duration of congenital deafness and the reorganization of the structural and functional changes of the brain in congenital deaf white cats. We will also study pCREB, BDNF and c-Fos expression changes of the auditory cortical neurons after CI and inhibition of the MAPK signal transduction pathway by immunohistochemical methods to determine that regulation of the MAPK pathway is the molecular mechanism of plastic reorganization in the auditory central nervous system. On the basis of these findings, we expect to clarify the brain plastic reorganization and mechanism in the congenital deaf after CI.

研究表明，人工耳蜗植入（CI）后听中枢神经系统发育状况和跨通道可塑性重组改变对康复效果产生明显影响，但耳聋持续时间与CI刺激后听中枢神经系统发育、结构和功能可塑性重组改变的具体关系及机制尚不清楚。解决此问题不仅能揭示CI后康复效果不同的原因和机制，为调整现有的CI决定策略提高康复效果提供新依据，而且能为研究依赖感觉输入的皮层发育可塑性提供新平台和证据。拟采用先天性耳聋白猫的锰增强磁共振成像(MEMRI)对耳聋持续时间与CI刺激后脑发育、结构和功能可塑性重组改变之间的关系进行研究，并通过免疫组化等方法检测耳聋CI刺激后听皮质神经元pCREB、BDNF和c-Fos表达水平及MAPK信号转导通路抑制后表达水平的改变情况，试图阐明MAPK通路调节是听中枢神经系统可塑性重组改变的分子机制。通过上述研究，达到阐明先天性耳聋CI刺激后脑可塑性重组改变及其机制的目的

人工耳蜗植入（CI）后听中枢神经系统发育状况和跨通道可塑性重组可能是CI术后康复效果的重要因素，而且耳聋持续时间可能对 CI 刺激后听中枢神经系统发育、结构和功能可塑性重组改变产生影响。本课题通过对幼猫进行持续皮下注射硫酸新霉素的方法建立了感音神经聋猫模型及致聋程度测试的方法和方案；与国内耳蜗公司合作，完成动物模型耳蜗电极设计、模具制作、完善修改并制作产品；探索并确定腹腔锰剂注射后锰增强MRI（MEMRI）是检测猫听觉通路改变的最佳方法；对不同年龄组致聋幼猫实施CI手术，通过MEMRI对耳聋持续时间与CI刺激后脑可塑性重组改变之间的关系进行研究，结果显示16周、24周、32周年龄组耳聋CI组幼猫双侧蜗神经核、斜方体背侧核信噪比分别低于正常对照组、高于耳聋组，并且16周龄耳聋CI组的双侧蜗神经核、斜方体背侧核信噪比高于24周龄耳聋CI组和32周龄耳聋CI组。该结果提示早期重度感音神经聋可能导致蜗神经核、斜方体背侧核发育障碍，而早期人工耳蜗电极植入及声音刺激可能有助于蜗神经核和斜方体背侧核的发育。采用多模态磁共振和脑网络分析方法对青少年语前聋患者的脑可塑性重组特点进行研究，结果显示患者听皮层内和视皮层内连接减低，语言相关脑区与视皮层之间连接减低，而听皮层与视皮层之间连接增加，同时视皮层与语言相关脑区的连接减低，而边缘系统和视皮层的连接增加，进一步说明先天性耳聋患者存在脑结构和功能的重组。综合上述结果，本研究为探讨耳聋 CI 刺激后听中枢神经系统可塑性重组改变及发生机制奠定了工作基础，且对于认识早期CI手术对耳聋患者康复效果的影响提供了重要的线索和依据。此外，本课题组建立动物耳蜗电极植入后脑改变检测方法和方案，为耳蜗电极设计改进研发提供了植入后康复效果评价方法和平台。发表SCI论文5篇，中文核心期刊论文3篇，培养博士和硕士研究生各3名。